Abstract
Focus on RAS codon 61 mutations in metastatic colorectal cancer (mCRC): A retrospective analysis.
Author
person
Francesco Schietroma
Oncologia Medica, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli–IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
info_outline
Francesco Schietroma, Annunziato Anghelone, Giustina Valente, Viria Beccia, Giulia Caira, Alexia Spring, Giovanni Trovato, Armando Di Bello, Anna Ceccarelli, Laura Chiofalo, Serena Perazzo, Maria Bensi, Michele Basso, Carmelo Pozzo, Lisa Salvatore, Maria Alessandra Calegari, Giampaolo Tortora
Full text
Authors
person
Francesco Schietroma
Oncologia Medica, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli–IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
info_outline
Francesco Schietroma, Annunziato Anghelone, Giustina Valente, Viria Beccia, Giulia Caira, Alexia Spring, Giovanni Trovato, Armando Di Bello, Anna Ceccarelli, Laura Chiofalo, Serena Perazzo, Maria Bensi, Michele Basso, Carmelo Pozzo, Lisa Salvatore, Maria Alessandra Calegari, Giampaolo Tortora
Organizations
Oncologia Medica, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli–IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy, Oncologia Medica, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli – IRCCS, Università Cattolica del Sacro Cuore, Italy, Roma, Italy, Oncologia Medica, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli–IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy, Oncologia Medica, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli – IRCCS, Università Cattolica del Sacro Cuore, Italy, Rome, Italy, Oncologia Medica, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
Abstract Disclosures
Research Funding
No funding received
None.
Background:
Nowadays,
RAS
mutational status remains a key determinant in mCRC patients’ therapeutic algorithm. Mutations involving codon 61 are rare, accounting for 1-4%, but have been recently identified with high frequency in ctDNA of pts with mCRC with secondary resistance to anti-EGFR mAbs, with a prevalence of 50% in the Chronos trial. Despite the growing clinical relevance of these mutations, evidence on clinicopathological features and prognosis of mCRC harboring codon 61
RAS
mutations is limited and relies on small retrospective studies. In 2014, a cohort study on 19 codon 61
KRAS
mutated (mt) mCRC reported clinicopathological and molecular features similar to
KRAS
codon 12 and 13 mt mCRC.
Methods:
This is an observational, retrospective, monocentric study, aiming to investigate and describe clinical phenotype and prognostic performance of codon 61
KRAS
or
NRAS
mt mCRC. Pts with codon 61
RAS
mt mCRC, treated at Fondazione Policlinico Gemelli between January 2013 and December 2021 were enrolled. Additional datasets of codon 61
RAS
wt mCRC (non-codon 61
RAS
mt,
BRAF
V600E mt and
RAS/BRAF
wt) treated at our Center during the same time period were used as comparators. Differences between groups for categorical variables were compared using Chi Square test. Endpoint for prognostic assessment was OS, estimated with the Kaplan-Meier method and compared using log-rank test. Statistical significance was set at
p
= .05.
Results:
50 pts with codon 61 mt
RAS
mCRC were included. The comparator dataset included 648 pts with codon 61
RAS
wt mCRC. Interestingly, 54% of codon 61
RAS
mt cohort developed peritoneal and/or ovary metastases during their disease history. Metastatic involvement of peritoneum or ovary was significantly more frequent in codon 61
RAS
mt mCRC compared to codon 61
RAS
wt mCRC (54
vs
28.5%,
p
= . 000163), significance was retained when comparing codon 61
RAS
mt to non codon 61
RAS
mt (54
vs
35.6%,
p
= .012495),
BRAF
V600E mt (54
vs
25%,
p
= .001286) and
RAS/BRAF
wt (54
vs
20.5%,
p
< .00001) cohorts. At a median FU of 96.2 m, mOS for codon 61
RAS
mt was significantly shorter compared to
RAS/BRAF
wt (26.9
vs
36.0 m, HR 0.56,
p
= .0006) while no significant difference was observed compared to non codon 61
RAS
mt (26.9
vs
30.2 m, p = .0993) and
BRAF
V600E mt (26.9
vs
22.6 m, p = .9124).
Conclusions:
We showed a statistically significant correlation between codon 61
RAS
mutations and metastatic involvement of peritoneum and ovary. This is the first evidence of an impact of
RAS
mutational status on metastatization pattern. In addition, our data showed a negative prognostic impact of codon 61
RAS
mt compared to
RAS/BRAF
wt mCRC, while no difference was observed compared to other non codon 61
RAS
mt and
BRAF
mt. These evidence warrant further validation in wider and prospective setting.
7 organizations
1 drug
1 target
Organization
Università Cattolica del Sacro CuoreOrganization
Romark LaboratoriesOrganization
RomeOrganization
ItalyDrug
anti-EGFR mAbs